International Cross-Age Consensus Guideline on Measurable Residual Disease Assessment in Acute Lymphoblastic Leukemia

Measurable residual disease (MRD) assessment is central to risk stratification, response evaluation, and relapse detection in acute lymphoblastic leukemia (ALL). However, substantial global variability in its methodology and implementation persists. Differences in sampling strategies, detection methods, reporting thresholds, and interpretation criteria hinder cross-trial comparability and clinical standardization. To address this, an international expert panel representing major pediatric and adult study groups and reference laboratories developed consensus recommendations, using a structured current-practices survey followed by a multi-round Delphi process. Consensus was achieved on 38 of 41 statements. Recommendations span three domains: pre-analytical requirements, technical and nomenclature standards, and MRD-based remission and relapse definitions. Bone marrow was endorsed as the reference specimen for MRD assessment, and MRD was prioritized over cytomorphology in cases of discordance. Principles for risk- and actionability-guided late MRD monitoring, confirmation of MRD reappearance, and MRD-informed relapse assessment were also defined. Among the key technical consensus statements, a standardized MRD assay nomenclature was adopted. Areas without consensus-namely, anticoagulant choice for PCR-based MRD, interpretation of isolated BCR::ABL1 reconversion, and the exclusive use of MRD to define remission-highlight ongoing biological and clinical complexity. This guideline, applicable across all ages, provides a practical framework to standardize MRD assessment in ALL and support MRD-guided clinical decision-making.

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Journal
Blood
Published
2026-11-10
DOI
https://doi.org/10.1182/blood.2026035088
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
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article

International Cross-Age Consensus Guideline on Measurable Residual Disease Assessment in Acute Lymphoblastic Leukemia

John P. Moppett, Pritha Dasgupta, Seth E. Karol, Jacques J. M. van Dongen et al.
Blood
Acute Lymphoblastic Leukemia research
article

International Cross-Age Consensus Guideline on Measurable Residual Disease Assessment in Acute Lymphoblastic Leukemia

John P. Moppett, Pritha Dasgupta, Seth E. Karol, Jacques J. M. van Dongen, Kerry Wall, Michelle J. Henderson, Julia Alten, Martin Schrappe, Toby N. Trahair, Michaela Kotrová, Emmanuelle Clappier, Vincent H. J. van der Velden, David T. Teachey, Gunnar Cario, Britta Kehden, Sabina Chiaretti, Barbara Buldini, Lewis B. Silverman, Andrea Biondi, Daniela Drandi, Carmelo Rizzari, Eva Froňková, Nicola Gökbuget, Irene Della Starza, Mireia Camós, Bela G. Patel, Monika Brüggemann, Csongor Kiss, Giovanni Cazzaniga, Nicolas Boissel, Adele Kay Fielding, Anke Schilhabel, Josep‐María Ribera, Jan Zuna, Sarah Elitzur, Cornelia Eckert, Nicholas James Short, Abhirupa Kar, Pfeifer Heike, Susana Rives
article en

Abstract

Measurable residual disease (MRD) assessment is central to risk stratification, response evaluation, and relapse detection in acute lymphoblastic leukemia (ALL). However, substantial global variability in its methodology and implementation persists. Differences in sampling strategies, detection methods, reporting thresholds, and interpretation criteria hinder cross-trial comparability and clinical standardization. To address this, an international expert panel representing major pediatric and adult study groups and reference laboratories developed consensus recommendations, using a structured current-practices survey followed by a multi-round Delphi process. Consensus was achieved on 38 of 41 statements. Recommendations span three domains: pre-analytical requirements, technical and nomenclature standards, and MRD-based remission and relapse definitions. Bone marrow was endorsed as the reference specimen for MRD assessment, and MRD was prioritized over cytomorphology in cases of discordance. Principles for risk- and actionability-guided late MRD monitoring, confirmation of MRD reappearance, and MRD-informed relapse assessment were also defined. Among the key technical consensus statements, a standardized MRD assay nomenclature was adopted. Areas without consensus-namely, anticoagulant choice for PCR-based MRD, interpretation of isolated BCR::ABL1 reconversion, and the exclusive use of MRD to define remission-highlight ongoing biological and clinical complexity. This guideline, applicable across all ages, provides a practical framework to standardize MRD assessment in ALL and support MRD-guided clinical decision-making.

Blood
Goethe University Frankfurt (DE), Universitat Autònoma de Barcelona (ES), Hospital Sant Joan de Déu Barcelona (ES), St. Jude Children's Research Hospital (US), University of Debrecen (HU), Children's Hospital of Philadelphia (US), The University of Texas MD Anderson Cancer Center (US), University of Padua (IT), Queen Mary University of London (GB), Charles University (CZ), Columbia University Irving Medical Center (US), Bristol Royal Hospital for Children (GB), Erasmus MC (NL), Christian-Albrechts-Universität zu Kiel (DE), Hôpital Armand-Trousseau (FR), Tata Medical Center (IN), Josep Carreras Leukaemia Research Institute (ES), Assistance Publique – Hôpitaux de Paris (FR), Centre for Biomedical Network Research on Rare Diseases (ES), Children's Cancer Institute Australia (AU), University Hospital Schleswig-Holstein (DE), Sydney Children's Hospital (AU), University Hospital Frankfurt (DE), Hôpital Saint-Louis (FR), Hospital Universitari Germans Trias i Pujol (ES), Birmingham Women’s and Children’s NHS Foundation Trust (GB), Institut de Recerca Sant Joan de Déu (ES), University of York (GB), University of Turin (IT), University of Milano-Bicocca (IT), Hull York Medical School (GB), Charité - Universitätsmedizin Berlin (DE), Sapienza University of Rome (IT)
Acute Lymphoblastic Leukemia research
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